This is the long-form version of Section 2, Article 39 (The longer you work night shifts, the higher the cardiovascular risk). While the original article only focuses on the calculations, this piece explains the underlying logic.
The question to be answered is: Can the body truly know what time it is? If so, why isn't working night shifts a matter of "getting used to it after pulling a few more all-nighters"?
I. There is indeed a ticking organ within the body
In the hypothalamus of the human brain, there is a small cluster of neurons called the suprachiasmatic nucleus, consisting of approximately twenty thousand cells. It serves as the master clock for the entire body.
Its ticking relies on a set of "clock genes" that inhibit each other. Two proteins called CLOCK and BMAL1 initiate the transcription of two other genes, PER and CRY. Once the PER and CRY proteins accumulate, they turn off the pair of proteins that activated them. Once these proteins are degraded, the cycle begins anew. One full cycle takes approximately 24 hours.
Therefore, this clock does not rely on observing the outside world to calculate time. If a person is placed in a room with absolutely no light, no clocks, and no social cues, this rhythm will continue to run. It is just that the period is not exactly 24 hours, and it will gradually drift day by day. The Nobel Prize in Physiology or Medicine in 2017 was awarded to the three researchers who discovered this molecular mechanism.
II. This clock synchronizes with light via a pathway that is not for "seeing"
In addition to the cells responsible for image formation, the retina contains a type of specialized photosensitive cells. They contain a pigment called melanopsin, which does not participate in seeing objects clearly but instead sends information about light intensity directly to the suprachromatric nucleus.
Thus, whether light can calibrate the biological clock has no direct relationship with whether the eyes can see objects. Some blind individuals who cannot see anything at all still have biological clocks that can be calibrated by light.
This is also the reason why Section 3, Article 2 (Maintain a fixed wake-up time, even on weekends) requires exposure to light in the morning.
III. The key lies in: There is more than one clock
The liver, intestines, heart, and adipose tissue each have their own set of peripheral clocks.
The master clock synchronizes via light. The peripheral clocks rely largely on "when you eat" to synchronize.
Under a normal routine, these two are synchronized. You see light during the day and eat during the day, so the master clock and the peripheral clocks point to the same time. Consequently, you usually do not even realize they are two separate systems.
IV. The problem with night shifts is not "staying up," but the decoupling of the two clocks
People working night shifts still see light during the day and still lead a daytime social life. Therefore, the master clock remains basically locked to the external diurnal cycle.
However, you are eating, working, and mobilizing metabolism during the biological middle of the night. The peripheral clocks are being pulled toward the other side.
This state is called circadian misalignment. The problem is not that you are getting a few fewer hours of sleep, but that the clocks throughout your body no longer align with each other.
V. And you cannot adapt to it
Some might think that one can always adapt to long-term fixed night shifts.
A review summarizing six studies measured the melatonin secretion rhythms of people working long-term fixed night shifts. The melatonin rhythm is the most reliable indicator for judging the state of the endogenous biological clock.
The result was: less than 3% of people achieved "complete" adaptation. Those who achieved "considerable" adaptation accounted for less than one quarter.
It remains the same regardless of how many years you have worked. The reason lies in the previous paragraph: you still have to see light during the day and participate in daytime social life; these cues are constantly pulling the master clock back.
Source: Folkard S (2008). Do permanent night workers show circadian adjustment? A review based on the endogenous melatonin rhythm. Chronobiology International. https://doi.org/10.1080/07420520802106835
6. How to know if it is the misalignment itself causing harm, not just lack of sleep
This is the most important layer to question in this entire matter. Night shift workers sleep less, eat irregularly, face high stress, and smoke more; all of these could be the true causes.
Fortunately, this can be isolated in a laboratory setting.
A study by Scheer et al. in the year 2009: 10 adults stayed in a laboratory for 10 days. The researchers artificially set "one day" to 28 hours, forcing their eating and sleeping to cycle through all stages of the biological clock. Four meals a day, with fixed caloric intake.
When behavior was misaligned with the biological clock by approximately 12 hours, the results were:
- Leptin decreased by 17% (leptin is the hormone that makes one feel full)
- Blood glucose increased by 6%, and this occurred even when insulin had already increased by 22%
- The diurnal rhythm of cortisol was completely reversed
- Mean arterial pressure increased by 3%
- Sleep efficiency decreased by 20%
The most critical point: among 8 individuals with sufficient data, 3 individuals had postprandial blood glucose enter the prediabetic range, in just 10 days.
Because the caloric intake was fixed and the experiment was controlled in a laboratory, these changes cannot be attributed to "lack of sleep" or "overeating." The misalignment alone is sufficient to cause these changes.
Source: Scheer FA, Hilton MF, Mantzoros CS, Shea SA (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment. PIMS, 106(11), 4453-4458. https://doi.org/10.1073/pnas.0808180106
VII. The First Thing You Can Change: Move Eating to the Daytime
Since peripheral clocks synchronize with mealtime, there is one direction worth trying: keep the night shift, but do not eat during the night.
A randomized controlled trial performed exactly this (Registration No. NCT02291952). 20 healthy individuals simulated a night shift and were randomly divided into two groups. One group followed the common habits of night shift workers, eating both at night and during the day. The other group ate only during the day.
Regarding the primary outcome, that report stated: in the group that ate at night, the central rhythm and the peripheral glucose rhythm became misaligned, and glucose tolerance worsened; these two issues did not appear in the group that ate only during the day.
The cardiovascular paper (a secondary analysis of the same trial) stated: in the group that ate at night, the cardiac vagal regulation index pNN50 dropped by 25.7%, RMSSD dropped by 14.3%, the LF/HF ratio reflecting sympathetic and vagal balance increased by 5.5%, and the pro-thrombotic factor PAI-1 increased by 23.9%. These changes did not occur in the group that ate only during the day.
However, this involved only 20 individuals, and it was a simulated night shift, not actual night shift workers.
A systematic review specifically looking for these types of randomized trials found only 4 trials after searching six databases. The results were not uniform: some trials saw improvements in fasting insulin and insulin resistance, while others did not; regarding high-density lipoprotein, none of the four trials saw any change; regarding postprandial glucose, the practice of fasting at night for 10.75 hours was indeed better than eating at night plus having a late-night snack. The authors of the review themselves stated that there are too few trials to generalize the findings.
Therefore, this is all that can be said for now: During night shifts, try to concentrate eating as much as possible during the daytime; this is supported by randomized trials, but the evidence is still thin. It costs no money and is not difficult to do; if you are willing to try, then try. There is a second thing worth trying, in the next section: moving the entire biological clock using light.
Source: Chellappa SL et al. (2021). Daytime eating prevents internal circadian misalignment and glucose intolerance in night work. Science Advances. https://doi.org/10.1126/sciadv.abg9910; Chellacy SL et al. (2025). Daytime eating during simulated night work mitigates changes in cardiovascular risk factors: secondary analyses of a randomized controlled trial. Nature Communications. https://doi.org/10.1038/s41467-025-57846-y; Wulandari F et al. (2026). Cardiometabolic status among shift workers under meal time regulation: A systematic review of randomized controlled trials. Nutrition and Health. https://doi.org/10.1177/02601060261464874
VIII. Can we just move the clock over?
Everything mentioned previously concerns how "misalignment is harmful." Conversely, what if we move the entire clock over to the night shift side—would that work?
In theory, yes, and it has been done. However, the requirements for light are an order of magnitude higher than most people imagine.
A study by Czeisler et al. in the year 1990: 8 young men worked night shifts for one week, comparing two different conditions.
Under the control condition, the nighttime used ordinary indoor lighting, approximately 150 lux. Lux is the unit of illuminance; a room with ordinary fluorescent lights is roughly one or two hundred. The result was that after six consecutive nights, the lowest point of body temperature still occurred around 3:30 AM. The lowest point of body temperature is a standard indicator for determining where the biological clock is pointing. This demonstrates that the biological clock remained completely unmoved.
Under treatment conditions, providing bright light of 7000 to 12000 lux at night, while sleeping in an almost pitch-black environment during the day. After four days, the lowest point of body temperature shifted to approximately 3 PM. It was as if the entire cycle had been flipped.
Source: Czeaksler CA, Johnson MP, Duffy JF, Brown EN, Ronda JM, Kronauer RE (1990). Exposure to bright light and darkness to treat physiologic maladaptation to night work. New England Journal of Medicine, 322(18), 1253-1259. https://doi.org/10.1056/NEJM199005033221801
Researchers recommend combining all three
First, the light at night must be bright enough. Working under ordinary fluorescent lights is equivalent to the "nothing happened" control group mentioned above. To be effective, specialized light therapy lamp boxes must be used.
Second, daytime sleep must be strictly light-proofed. Blackout curtains plus eye masks. The experiment mentioned above implemented both "bright light at night" and "near-total darkness during the day" together; it was not a choice between the two.
Third, wear sunglasses on the way home from work. This is the easiest measure to overlook. In a 1994 experiment with 50 participants, bright light and dark goggles each had an effect, and combining them worked best. Without goggles, the biological clock shifted only earlier, rather than in the direction needed for daytime sleep. See the sources for Section 2, Item 39 (if you can transfer out of night shifts, do it sooner).
Site note: In this experiment, temperature rhythms could align with daytime sleep through either phase advances or phase delays. Without goggles, only advances occurred. The paper does not establish that every night worker must adapt by delaying their rhythm. Study abstract
Why the third item is so critical depends on how light functions: the same light, when falling at different times, pushes the biological clock in opposite directions. Seeing light before the lowest body temperature point pushes the clock backward (later); seeing light after the point pulls the clock forward (earlier).
When you head home after a night shift, you are precisely after the lowest body temperature point. What this morning light does is in the exact opposite direction of what sitting in front of a light box does all night.
Possible in the Lab, Impossible in Daily Life
In the laboratory, those individuals do not leave the room for an entire week. In reality, you must live your daytime life on your days off—picking up children, spending time with family, running errands. Every time you do this, the clock is pulled back. This is the source of the figure in Section 5: less than 3% of long-term fixed night-shift workers can fully adapt.
Therefore, in the real world, the goal is usually not to achieve a complete reversal, but rather to shift only a portion, allowing the clock to settle at an intermediate position where you are "awake enough during work hours, without completely ruining your days off."
How much can be achieved in reality
A meta-analysis summarizing 11 studies: light therapy increases the total sleep time of shift workers by approximately 32.5 minutes and improves sleep efficiency by approximately 2.91. The effective dose is 900 to 6000 lux, for at least 1 hours per night.
Another laboratory study used intermittent bright light. The melatonin secretion of the treatment group overlapped with the scheduled sleep period by 4.90 hours, whereas the control group only had 2.62 hours (P=0.002). The decline in cognitive performance observed in the control group during the last night shift was suppressed in the treatment group. In the conclusion, the authors explicitly stated that this approach still needs to be validated on actual shift workers.
Sources: Zhao C, Li N, Miao W, He Y, Lin Y (2025). A systematic review and meta-analysis on light therapy for sleep disorders in shift workers. Scientific Reports. https://doi.org/10.1038/s41598-024-83789-3; Lammers-van der Holst HM et al. (2021). Efficacy of intermittent exposure to bright light for treating maladaptation to night work on a counterclockwise shift work rotation. Scandinavian Journal of Work, Environment & Health. https://doi.org/10.5271/sjweh.3953
Something that has never been tested
"If the clock is moved correctly, will cardiovascular risk decrease accordingly?" — No trial has tested this.
What is already known is that misalignment is harmful, which was demonstrated by the experiment in Section 6. However, this does not mean the reverse—that "moving it correctly makes it safe"—is true. Furthermore, whether the back-and-forth struggle of moving the clock back during days off is good or bad has also never been tested.
The endpoints of the two strategies mentioned above—one focusing on metabolic and cardiovascular indicators, and the other on sleep—do not reach the level of disease incidence and mortality.
IX. What this article does not discuss
Exactly how much night shifts increase cardiovascular risk, and how to calculate it by number of years, can be found in Section 2, Item 39 (the longer you work night shifts, the higher the cardiovascular risk).
How to catch up on sleep after staying up late can be found in Section 2, Item 38 (catch up on sleep the following night after staying up late).
How long to sleep at night and maintaining a regular schedule can be found in Section 2, Item 13 (sleep approximately 7 hours per night, with a fixed schedule).
Morning light exposure and a fixed wake-up time can be found in Section 3, Item 2 (fixed wake-up time, even on weekends).
